DSpace Collection:http://cmuir.cmu.ac.th/jspui/handle/6653943832/75862018-12-19T07:11:12Z2018-12-19T07:11:12ZDevelopment of Novel Polymeric Micelles as Drug Delivery Systems for CurcuminOrnchuma Naksuriyahttp://cmuir.cmu.ac.th/jspui/handle/6653943832/628972018-12-11T07:44:31Z2015-12-01T00:00:00ZTitle: Development of Novel Polymeric Micelles as Drug Delivery Systems for Curcumin
Authors: Ornchuma Naksuriya
Abstract: Curcumin is a natural yellow phenolic compound which presents in many kinds of herbs, especially in turmeric (Curcuma longa L.). It has been reported in many studies that curcumin is a natural antioxidant and anticancer agent. However, its pharmaceutical applications as therapeutic agent are limited because of its poor aqueous solubility and chemical instability under alkaline condition. Therefore, the aims of this present study were to develop and explore the advantages of novel polymeric micelles composed of block copolymers of methoxy poly(ethylene glycol) (mPEG) and N–(2–hydroxypropyl) methacrylamide (HPMA) modified with aromatic benzoyl side groups as nanocarriers for solubility, stability, and anticancer activity enhancement of curcumin. In first stage of study, the physicochemical characteristics and biological activity of curcumin were investigated. The antioxidant activity of curcumin in comparison with three important natural antioxidants, namely gallic acid, ascorbic acid, and xanthone, were performed on free radical scavenging action. The results indicated that the activities of these compounds were dose–dependent. The 50% effective concentration (EC50) of curcumin was found to be 11 µg/mL (30 µM). Curcumin showed significantly higher antioxidant activity than ascorbic acid and xanthone but less than gallic acid, indicating that antioxidant capacity of curcumin is higher than most of the other natural antioxidants which are ascorbic acid and xanthone. The solubility study showed that curcumin has a poor solubility in water, hexane, and toluene, but it is well soluble in polar aprotic solvent and alcohols. The kinetic degradation of curcumin under various conditions (pH, temperature, and dielectric constant of the medium) was investigated. To fully solubilize curcumin and to prevent curcumin precipitation that occurs when low volume fractions of co–solvent are present, a 50:50 (v/v) buffer/methanol mixture was used as standard medium to study its degradation kinetics. The results showed that the degradation of curcumin followed first order kinetics. It was further shown that an increasing pH, temperature, and dielectric constant (or increasing aqueous buffer volume fraction) of the medium resulted in an increase in degradation rate. Curcumin showed rapid degradation due to autoxidation in phosphate buffer pH = 8.0 with a rate constant of 280 × 10-3 h-1, corresponding with a half–life (t1/2) of 2.5 h. Dioxygenated bicyclopentadione was identified as the final degradation product as evidenced from liquid chromatography electrospray ionization mass spectroscopy (LC–ESI–MS) analysis.Polymeric micelles have shown great promises in solubilization, stabilization, and delivery of hydrophobic drugs for cancer treatment. Therefore, the amphiphilic block copolymers, ω–methoxy poly(ethylene glycol)–b–(N–(2–benzoyloxypropyl) methacrylamide (PEG–HPMA–Bz, molecular weight of PEG = 5000 Da, molecular weight of HPMA–Bz block from 18000 – 43800 Da), were synthesized. One polymer with molecular weight of 28300 Da had the lowest polydispersity index and was obtained in a high yield. This polymer was used in this study and compared with different aromatic substituted micelle forming polymers, (ω–methoxypoly(ethylene glycol)–b–(N–(2–hydroxypropyl) methacrylamide dilactate) (PEG–HPMA–DL)which has dilactate side chains and ω–methoxy poly(ethylene glycol)–b–(N–(2–benzoyloxy) methacrylamide)–co–(N–(2–lactoyloxypropyl) metha-crylamide) (PEG–HPMA–Bz–L) which has monolactate (75%) and benzoyl (25%) side groups. A simple micellar formation was used by a fast heating method for PEG–HPMA–DL and PEG–HPMA–Bz–L, whereas a nanoprecipitation method was used to obtain micelles of PEG–HPMA–Bz. The average particle sizes of curcumin–loaded polymeric micelles ranged from 46 to 85 nm, and the micelles showed spherical shapes. The PEG–HPMA–Bz micelles with benzoyl side groups (100%) gave the best solubili-zation and the curcumin solubility increased up to 2 mg/mLat a polymer concentration of 10 mg/mL. Fourier transform infrared spectroscopic analysis, x–ray diffraction patterns, and differential scanning calorimetry confirmed that curcumin was successfully entrapped in the micelles. The PEG–HPMA–DL micelles without aromatic benzoyl group almost fully released curcuminin20 days, whereas PEG–HPMA–Bz and PEG–HPMA–Bz–L released in the same time (27% and 50% of their curcumin loading, respectively). This release profile pointed a greater affinity of curcumin for polymeric micelles with aromatic groups. More importantly, curcumin in PEG–HPMA–Bz, PEG–HPMA–Bz–L and PEG–HPMA–DL micelles was about 300, 8, and 2 times, respectively, more stable than curcumin in phosphate buffer pH = 8.0. Curcumin–loaded PEG–HPMA–Bz micelles also showed the best stabilization of curcumin (80% of curcumin remaining) with the similar particle size as the first day (50 – 60 nm) after storage at 4, 30, and 40°C for 90 days, whereas curcumin–loaded PEG–HPMA–Bz–Land PEG–HPMA–DL micelles were less stable. The greater loading capacity, slower sustained release, and greater stabilization of the PEG–HPMA–Bz micelles are probably due to 𝜋–𝜋 stacking between the aromatic groups of curcumin and benzoyl groups of the polymer.Moreover, the interaction of proteins and all three polymeric micellar systems investigated in this thesis did not cause aggregation of the polymericmicelles. It was demonstrated that all three curcumin–loaded polymeric micelles showed no toxicity towards normal cells (red blood cells and peripheral blood mononuclear cells (PBMCs)), but provided good cytotoxic effects against human ovarian carcinoma cells (OVCAR–3), human cervical adenocarcinoma (HeLa), human colorectal adenocarci-noma (Caco–2), human breast adenocarcinoma (MCF–7), human lymphoblastic leukemia (Molt–4), and human chronic myelogenous leukemia (K562). Additionally, curcumin–loaded polymeric micelles were effectively internalized into K562 cells as demonstrated by fluorescence microscopy. It was shown that curcumin–loaded polymeric micelles induced cell cycle arrest at G2/M phase in K562 cells, and they also suppressed Wilms’ tumor 1 protein levels to 43 – 47%. In conclusion, the results in this study suggest that the enhanced solubility and stability of curcumin by loading into PEG–HPMA–Bz micelles is a promising nanodelivery system to provide suitable nanocarriers for further pharmaceutical and clinical development for cancer therapy.2015-12-01T00:00:00ZAdhesion and Inhibition of Streptococcus mutans by Electrospun Fibers Containing Propolis for Fast Dissolving Dosage FormChawalinee Asawahameชวาลินี อัศวเหมhttp://cmuir.cmu.ac.th/jspui/handle/6653943832/459592018-03-27T03:42:30Z2014-07-01T00:00:00ZTitle: Adhesion and Inhibition of Streptococcus mutans by Electrospun Fibers Containing Propolis for Fast Dissolving Dosage Form
Authors: Chawalinee Asawahame; ชวาลินี อัศวเหม
Abstract: The objective of this study was to prepare orally fast dissolving fibers using anelectrospinning process with hydrophilic polymers.Propolis extract was used as an active ingredient, volatile oils such as eucalyptus oil, methyl salicylate, menthol and thymol were used as flavoring agents, while Tween 80 was used as wetting agent in the formulation. The antimicrobial activity of propoliselectrospun fibers against Streptococcus mutans which is the major bacteria for inducing tooth decay and plaque formation was studied. The inhibition of adherence of S.mutansto smooth glass surface by propoliselectrospun fibers was also studied and compared with commercial mouthwash solutions.
Three kinds of hydrophilic polymers were studied using polyvinyl pyrrolidone (PVP), polyvinyl alcohol (PVA)andhydroxypropyl cellulose (HPC) to arrive at a suitable polymer and its optimum condition for fiber formation. This investigation used different types and molecular weights of polymers (PVP K90, PVP K30, PVA MW 85,000-146,000, PVA MW 47,000 and HPC MW 370,000) to influence the spinnability of the polymer solution, and thus the morphology of the electrospun fibers. The morphology of electrospun fibers was influenced by various solution parameters (viscosity, conductivity, surface tension) and process parameters (electric field strength, flow rate, collector type). It was found that PVP K90 at 8–10% (w/v) in ethanol with the following spinning conditions,generated electrospun fiberswith appropriate quality and stability:a distance between the needle tip and the collector of 15 cm, a voltage supply of 15kV, anda feed rate at 2 mL/hr.
Propolis-PVP electrospun fibers were successfully prepared using the above electrospinning technique. Incorporated propolisup to 5% (w/v) in PVP K90 polymer solution was able to produce smooth, uniform and free-bead electrospun fibers with diameters ranging around 1.2 – 1.4 m. 1% (w/v) Tween80 was used as wetting agent for improved wettability of electrospun fibers which were incorporated into the propolis.
Propolis-PVP electrospun fibers can be disintegrated and dissolved in small amounts of water.The antibacterial activities from Propolis-PVP electrospun fibers against S. mutans when tested through agar diffusion revealed an inhibition zone when tested with a concentration of propolis from electrospun fibers equivalent to 10 MIC and above (propolis extract used in this study showed MIC at 1.172 mg/mL). Electrospun fibers of 5% (w/v) propolis with 8% (w/v) PVP electrospun fibers with or without additives and Tween80,were tested at a concentration of propolisequivalent to 0.6 MIC and 1 MIC an this reduced the adherence of S. mutanstoa smooth glass surface with more than 50%. The resultproved that propolis extract in electrospun fibers at 0.6 and 1 MIC aremore effective thancommercial mouthwash solutions containing natural essential oils as active ingredientsthat were free from chemical antiseptic substances but were, however, less effective than the mouthwash solutions containingsome chemical substances as antiseptic agents.
In conclusion, the present study has demonstrated that propolis-PVP electrospun fibers can be used as fast dissolving fibers to control S. mutans in oral cavities. Propolis-PVP electrospun fiber matscan be used as an alternative anticariogenic agent,and in a newsolid dosage form.2014-07-01T00:00:00ZFactors Affecting Cannabinoid Contents for Classification of Hemp (Cannabis sativa L.) in Northern ThailandPrapatsorn Tipparatประภัสสร ทิพย์รัตน์http://cmuir.cmu.ac.th/jspui/handle/6653943832/459572018-03-27T03:28:22Z2014-08-01T00:00:00ZTitle: Factors Affecting Cannabinoid Contents for Classification of Hemp (Cannabis sativa L.) in Northern Thailand
Authors: Prapatsorn Tipparat; ประภัสสร ทิพย์รัตน์
Abstract: The Thai government has recognized the possibility for legitimate cultivation of hemp. The study of certain cannabinoid characteristics is necessary in establishing criteria for regulation of cannabis cultivation in Thailand. For this purpose, factors affecting characteristics of cannabinoid composition of Thai-grown cannabis were investigated. Plants were cultivated from seeds derived from the previous studies under the same conditions. Three hundreds and seventy two cannabis samples from landraces, three different trial fields and the seized marijuana were collected and analyzed for THC, CBD and CBN contents by GC-FID. The results showed that the cannabis grown during March-June, 2008 which had longer vegetative stages and longer photoperiod exposure, had higher cannabinoid contents than those grown in August. The male plants grown in the trial fields had the range of THC contents from 0.722-0.848 %d.w and average THC/CBD ratio of 1.9. Cannabis in landraces at traditional harvest time of 75 days had a range of THC contents from 0.874-1.480 %d.w and an average THC/CBD ratio of 2.6. The THC contents and THC/CBD ratios of cannabis in the second generation crops grown in the same growing season were found to be lower than those grown in the first generation, unless fairly high temperatures and a lesser amount of rainfall were present. The average THC content in the seized fresh marijuana was 2.068% d.w while THC/CBD ratios were between 12.6 and 84.09, which is 10-45 times greater than those of similar studied cannabis samples from the previous study.
Thus, the use of the THC/CBD ratio or log10 values of THC/CBD may give an advantage for distinguishing hemp from marijuana. Furthermore, at the harvest time of 70-75 days which is appropriate time for collecting good quality fiber, the cannabis plants grown in landraces and the trial fields appeared to have the mean actual THC content less than 1%. Therefore, the permitted THC content of 0.5-1% in cannabis for fiber usage would be acceptable.
Moreover, both chemical and physical characters of Thai-grown cannabis were studied to provide information for breeders to discriminate their phenotypes and accessions in order to select the low intoxicant with high fiber producing cultivars. The cannabinoids on the basis of THC, CBD and CBN content of 750 plants from eight accessions derived from five local cannabis variants were analyzed individually and their morphological features were also determined. According to the individual plants belonging to the same accessions showing distinct THC/CBD ratios were classified into different phenotypes, it is impossible to classify only single plant for defining the phenotype or determine cannabinoid contents on the single analysis. The minimum number of 50 plants is considerable as representative to be sampled. The THC content was found to correlate negatively to their physical characters such as plant height, stem diameter and fiber weight. The principal component analysis showed that the fiber weight, core weight and stem diameter of the plant as well as the chemical features such a THC content, CBD content, THC/CBD ratio and log10(THC/CBD ratio) explained most of the total variation which could distinguish accession and phenotype of the cannabis plants. The stepwise discriminant analysis confirmed that the cannabinoids and some physical properties could be used to classify the phenotype of cannabis plants into drug, intermediate and fiber types as well, whereas the accessions of the cannabis could not be discriminated clearly by using only their physico-chemical parameters.
Pre-defined phenotype of cannabis plants based on the log10 (THC/CBD ratio) were also evaluated with the developed multiplex PCR method. Although the total relative accuracy of identification obtained was only 94%, the pre-defined as fiber and drug type exhibited the 100% of identify. Therefore, the use of the log10 (THC/CBD ratio) to classify the phenotype of cannabis plant is preferable.
From the chemical fingerprints study, the results not only revealed the difference between the authorized cannabis grown for fiber usage and marijuana but also indicated that some terpenoids especially sesquiterpenoids and some cannabinoids could be used to distinguish the marijuana from the cannabis grown for fiber usage as well as among the variants
Nonetheless, more samples should be further investigated to confirm this conclusion as well as the genetic relationships among the cannabis accessions grown in northern Thailand should be performed in further study. However, the expanded information provided by the current study will assist the development of criteria for regulation of hemp cultivation in Thailand.2014-08-01T00:00:00Zรูปแบบและปัจจัยที่ส่งผลต่อความเหมาะสมในการสั่งใช้ยา ปฏิชีวนะ สำหรับผู้ป่วยโรคติดเชื้อทางเดินหายใจส่วนบน ในโรงพยาบาลส่งเสริมสุขภาพตำบลในเขตอำเภอสามเงา จังหวัดตากสุรศักดิ์ สวนทองhttp://cmuir.cmu.ac.th/jspui/handle/6653943832/459342018-03-26T07:32:54Z2557-07-01T00:00:00ZTitle: รูปแบบและปัจจัยที่ส่งผลต่อความเหมาะสมในการสั่งใช้ยา ปฏิชีวนะ สำหรับผู้ป่วยโรคติดเชื้อทางเดินหายใจส่วนบน ในโรงพยาบาลส่งเสริมสุขภาพตำบลในเขตอำเภอสามเงา จังหวัดตาก
Authors: สุรศักดิ์ สวนทอง
Abstract: This descriptive study aimed to study antibiotic prescribing patterns for patients with upper respiratory tract infections among healthcare personal at Tambon health promoting hospitals in Samngao district, Tak province; and to identify factors influencing the antibiotic prescribing behaviors. The target samples were 440 patients with upper respiratory tract infection selected by multistage sampling. Their patient information records were retrieved from JHCIS database at Tambon health promotion hospitals in Samngao district, Tak province during Octobert 1, 2011 to September 30, 2012. The prescribing patterns were compared against the standard criteria of the National Antibiotic Smart Use program (ASU).
The results showed that almost half of the patient received antibiotics for upper respiratory tract infection treatment. Of those receiving antibiotics, 40.68% were prescribed inappropriately as 38.18% of them received antibiotics without appropriate indication, especially found in pharyngitis and tonsillitis cases. Factors influencing the inappropriate prescribing behaviors included disease condition and prescriber’s length of experience. Patients with otitis media were significantly more likely to received inappropriate antibiotic prescription than those with common cold, OR otitis media/ common cold = 79.20 (95% CI = 9.87-635.49), p ≤. 0.001. Patients with tonsillitis were significantly
more likely to received inappropriate antibiotic prescription than those with common cold, OR tonsillitis / common cold = 40.00 (95% CI = 17.86-89.54), p ≤. 0.001. Patients with pharyngitis were significantly more likely to received inappropriate antibiotic prescription than those with common cold, OR pharyngitis / common cold = 31.74 (95% CI = 17.42-57.84), p ≤. 0.001. Patients with sinusitis were significantly more likely to received inappropriate antibiotic prescription than those with common cold, OR sinusitis / common cold = 21.60 (95% CI = 2.17-214.40), p =. 0.009. Prescribers having more than 20 years and having 11-20 years of experience were more likely to inappropriately prescribe antibiotic than those having less than 10 years of experience, significantly; OR > 20 years / <10 years = 3.10 (95% CI = 1.86-5.17), p ≤. 0.001 and OR 11- 20 years / <10 years = 3.02 (95% CI = 1.75-5.22), p ≤ 0.001.
The study findings could be concluded that the majority of healthcare personal at Tambon health promoting hospitals in Samngao district, Tak province inappropriately prescribed antibiotic for patients with upper respiratory tract infection. The major reason might be an inability to make clear disease diagnosis in order to make decision for prescribing antibiotic appropriately. Therefore, they are in need for better knowledge about diagnosis, dose and duration of antibiotic use, especially among those with more than ten years of working experience.2557-07-01T00:00:00Z